Detox - Biotransformation Pathways

The Biotransformation/Detox System Is A Big Topic

To understand the biotransformation system is overwhelming for most people. Researchers are only just beginning to get a grasp of it. However, we know enough about this magnificent system to make use of the data in the process of getting well after being exposed to a water-damaged building. The biotranformation system is used by all cells of the body, but some cells like the liver, intestines, kidney, skin and lungs are busy beavers when it comes to transforming hormones, toxins and other substances to either transform them into something useful or remove them from the body. At least that is the idea of the system. It is basically a recycling, and trash removal system. However, sometimes the system does not work up to par and may make more toxic items or may not be able to remove items sufficiently due to genetics, or due to mycotoxins decreasing the activity and functionality of this beautiful system. Luckily, we can use nutrition through food and supplements, herbs, lifestyle changes and other healing modalities to support this biotransformation system and help increase the proper removal of mycotoxins and other toxins from the body.

When we don't have adequate glutathione (it is not a lone player, just an important player in the game) the mitochondria in our cells are overwhelmed by reactive oxyden species, and they start putting out danger repsonse signals as well as decreasing energy output which makes us tired. The singals they put out cause inflammation and havoc in the body. Therefore availability of glutathione and ability to recycle and use glutatione is very important.

For detailed analysis of this intricate system, read more here.

At the above link you will find data on supporting methylation, glutathione conjugation, glucuronidation, sulfation, amino acid conjugation, and acetylation.

Or skip all that for the moment, and I will give you some basics on how we can support this process. Things that will help most, or many of the people who have been exposed and are sensitive to water-damaged buildings.

Glutathione

I am bringing up glutathione here as it is an amazing antioxidant that is used all through-out the many steps of cellular detox to keep the free radicals down. It is also necessary for glutathione conjugation which is one of the major detox processes in the body. Therefore, for anyone with a toxin issue, their bodies access to glutathione is very important. The first thing I usually have a person do after starting binders, or at the same time, is to take/enhance production of glutathione. Mycotoxins can interfere in the process of making and using glutathione, so simply supplying it, or N-acetyl-cysteine can be a big help in the beginning. The individual is often so sick by the time I work with them, that they are having trouble making enough glutathione, and rather than giving them the materials to make glutathione, I find they do better by simply replacing it for a while. (using forms that are more readily available) Additionally using methods to make more glutathione by providing a healthy diet, and using the supplement N-acetyl cysteine is beneficial, and is generally started as soon as possible.  Be aware that glutathione is used by the body to detoxify itself of many things. So while you are increasing the ability to remove mycotoxins, you are also increasing removal of other toxins. This can be overwhelming to remove toxins from the tissues if done too fast. If the person reacts, back off and go slower. Reactions can also take place when a person is not consistent in taking supplements that remove toxins. So, they have to be taken on a set schedule.

An individual may need to support other conjugation activities such as acetylation, sulfation, methylation, glucuronidation, amino acid conjugation or even modulate CYP P450 enzyme activity depending on their genetics, signs, symptoms, and lab values. It is too much for me to go into detail on this page, but please look further into the biotransformation system, and how to support the various aspects of it.

I also have an entire page devoted to glutathione if you want to know more about it.

 

Glutathione And mycotoxins

Glutathione is necessary for both phase 1 and phase 2 of our detoxification pathways. Glutathione is necessary to remove many types of mycotoxins. The aflatoxin AFB1 can be metabolized by the Cytochrome P450 system to AFB1-8,9-epoxide (AFBO) which can become quite hazardous OR it can be excreted via the urine with the use of glutathione. Glutathione S-transferase is needed to conjugate AFBO and excrete it in the urine. If AFBO is not conjugated and excreted it can cause toxicity including cancer. This means both gluathione, and the enzyme used to conjugate the mycotoxin to glutathione, and glutathione have to be available.

 

Glutathione is A Master Antioxidant

Glutathione scavenges free radicals and helps regenerate other antioxidants such as vitamins C and E. Glutathione's antioxidant and detoxification abilities play a major role in the every day function of cells. Exposure to mycotoxins in humans requires the production of glutathione on an “as needed” basis. Research suggests that some of these mycotoxins themselves can decrease the formation of glutathione due to decreased gene expression of the enzymes needed to form glutathione. Mycotoxin-related compromise of glutathione production can result in an excess of oxidative stress as well as loss of toxin removal, both leading to tissue damage and systemic illness. This is why it is so important for people with mold associated illness to address low glutathione levels.

 

More Details on Glutathione

Glutathione is the star detoxifier in our body. It is a small protein composed of three amino acids - cysteine, glutamine, and glycine. It is synthesized in the body, but toxins, poor diet, and pollution, as well as stress, aging, trauma, infections and radiation all deplete glutathione levels. The sulfhydryl group (SH) of cysteine serves as a proton donor and is responsible for the biological activity of glutathione. Cysteine is the rate-limiting factor in cellular glutathione synthesis, since this amino acid is relatively rare in food. (cysteine is supplemented as N-acetyl cysteine or NAC) Normally glutathione is recycled in the body, except when the toxic load becomes too great, and in the case of mycotoxins they have been shown to decrease glutathione levels in the body.

 

Glutathione Conjugation And Glutathione S-Transferase

Glutathione conjugation is probably the most important detoxification pathway for industrial toxins and carcinogens and 60% of toxins excreted in the bile are excreted in this way. Glutathione conjugation also produces water-soluble mercaptates which are excreted via the kidneys.

Glutathione conjugation is a major route of memoval of mycotoxins. Glutathione is conjugated (attached) to the toxin and removed from the body through this process. The process requies an enzyme call glutathione transferase for this to take place. 33%-50% of people are missing normal GSTM1 (a gene) function that controls glutathione S-transferase. This gene needs to be available to enable adequate glutathione conjugation. So, these folks who are low in GSTM1 will have even more trouble conjugating mycotoxins with glutathione. If you have a 23 and me genetic test, look up rs366631, and if you are AA: GSTM1 =low/ lower enzyme activity likely, AG: GSTM1= normal enzyme activity is likely, GG :GSTM1= normal enzyme activity is likely. Now don't get worried if you are AA. We don't know everything there is to know about genetics and it is possible other aspects of your biotransformation system may help pick up slack. It even appears that GSTM2 may pick up part of the slack from a decreased activity of GSTM1.  Lots of theories, and some studies, but waiting for some definitive reasearch.

Example of alternate detox pathways: The formation of glutathione conjugates, as well as glucuronide and sulfate conjugates to the mycotoxin called aflotoxin have been described in some animals, and many metabolites of aflatoxin can all undergo glucuronidation, and sulfation in addition to glutathione conjugation. Spirit has many pathways to the same destination.

 

Glutathione Supplements & Supporting Glutathione Production In The Body

Most forms of oral gluathione are digested by the body and otherwise not absorbed. However, even if they are digested, the amino acids can be reused by the body to make glutathione again, so not a total waste. However, it is more expensive than buying the amino acids cysteine, glutamine and glycine.

Acetyl-Glutathione is available from  Allergy Research, and is a form of oral glutathione that is stable in the stomach and gastrointestinal tract and well absorbed. Liposomal glutathione is another form of glutathione with good absorption.

Nebulized (inhaled) glutathione is also used but should only be used under the care of a trained practitioner. It may cause a broncho-constriction reaction in some of your toxic patients.

 

Eating To Raise Glutathione

Anything that contains the sulfur amino acid called cysteine will be beneficial as it is the rate limiting amino acid necessary for making gluathione. Gluathione is made of the amino acids glycine, glutamine and cysteine.

Cysteine is an amino acid and can be found in most high protein foods such as meat,  eggs, dairy, also good amounts in nuts and seeds, high in sunflower seeds, high in oats, and also in fish, dairy foods, legumes, asparagus, avacado, spinach.

Whey from making cheese or concentrated whey products are rich in cysteine: The whey protein needs to be bioactive and made from non-denatured proteins ("denaturing" refers to the breakdown of the normal protein structure). Use non-pasteurized, organic, non-denatured  whey, or whey protein. I use to make cheese when I milked goats and had tons of whey. It can be added to smoothies, drank as is, or added to anything where you need moisture in a dish you are making.  What is on the market is a concentrated whey product. This study found whey protein isolate increased plasma glutathione and total antioxidant capacity.

The body can also make cysteine, but does not always make enough. It is considered a semi-essential amino acid. Sulfur-rich foods are needed to make cysteine. Sulfur rich foods are onions, garlic, leeks, all cruciferous vegetables such a broccoli, collards, cabbage, brussel sprouts, kale, cauliflower, kohlrabi, watercress, etc. The glucosinolates such as glucoraphanin in the cruciferous vegetables is changed by myorsinase (in the plant or made by colon bacteria) to sulforaphane that is then conjugated with our bodies glutathione and ultimately made into a sulforaphane N-acetlycysteine using our bodies glutathione,  and may exhibit goitrogenic or antithyroid activity. Although we are providing sulfurs by eating Cruciferae plants (mustard family), we are also using our glutathione in the metabolism of the plant materials. Is this an issue? I really can't say.